Method of diagnosing ovarian endometriosis

Abstract

Disclosed are methods of diagnosing ovarian endometriosis using differentially expressed genes. Ovarian endometriosis associated genes identified herein or their gene products are useful as a diagnostic markers for identifying or detecting ovarian endometriosis. Also disclosed are methods of screening compounds serving as agents for treating ovarian endometriosis, and methods of treating ovarian endometriosis and method or vaccinating a subject against ovarian endometriosis.

1 . A method of diagnosing ovarian endometriosis or a predisposition of developing ovarian endometriosis in a subject, comprising determining the expression level of an ovarian endometriosis-associated gene in a subject-derived biological sample, wherein an increase or decrease of said expression level compared to a control level of said gene indicates that said subject suffers from or is at risk of developing ovarian endometriosis.  
     
     
         2 . The method of  claim 1 , wherein said ovarian endometriosis-associated gene is selected from the group consisting of OEX 1-97 and 186-242, wherein an increase in said level compared to a normal control level indicates said subject suffers from or is at risk of developing ovarian endometriosis.  
     
     
         3 . The method of  claim 2 , wherein said increase is at least 10% greater than said normal control level.  
     
     
         4 . The method of  claim 1 , wherein said ovarian endometriosis-associated gene is selected from the group consisting of OEX 98-185, wherein a decrease in said level compared to a normal control level indicates said subject suffers from or is at risk of developing ovarian endometriosis.  
     
     
         5 . The method of  claim 4 , wherein said decrease is at least 10% lower than said normal control level.  
     
     
         6 . The method of  claim 1 , wherein said method further comprises determining the expression level of a plurality of the ovarian endometriosis-associated genes.  
     
     
         7 . The method of  claim 1 , wherein the expression level is determined by any one method selected from the group consisting of: 
 (a) detecting the mRNA of an ovarian endometriosis-associated gene;    (b) detecting the protein encoded by an ovarian endometriosis-associated gene; and    (c) detecting the biological activity of the protein encoded by an ovarian endometriosis-associated gene.    
     
     
         8 . The method of  claim 7 , wherein said expression level is determined by detecting hybridization of an ovarian endometriosis-associated gene probe to a gene transcript in said subject-derived biological sample.  
     
     
         9 . The method of  claim 8 , wherein said hybridization step is carried out on a DNA array.  
     
     
         10 . The method of  claim 1 , wherein said biological sample is a tissue sample and comprises an epithelial cell.  
     
     
         11 . The method of  claim 1 , wherein said biological sample is a tissue sample comprising an endometrial cyst cell.  
     
     
         12 . The method of  claim 11 , wherein said biological sample is a tissue sample comprising an epithelial cell from an endometrial cyst.  
     
     
         13 . An ovarian endometriosis reference expression profile, comprising a pattern of gene expression of two or more genes selected from the group consisting of OEX 1-242.  
     
     
         14 . An ovarian endometriosis reference expression profile, comprising a pattern of gene expression of two or more genes selected from the group consisting of OEX 1-97 and 86-242.  
     
     
         15 . An ovarian endometriosis reference expression profile, comprising a pattern of gene expression of two or more genes selected from the group consisting of OEX 98-185.  
     
     
         16 . A kit comprising one or more detection reagents which binds to one or more nucleic acid sequences selected from the group consisting of OEX 1-242.  
     
     
         17 . An array comprising one or more nucleic acids which bind to one or more nucleic acid sequences selected from the group consisting of OEX 1-242.  
     
     
         18 . A method of diagnosing ovarian endometriosis in a subject, comprising the steps of: 
 (1) determining the expression level of a TFPI-2 protein in a subject-derived biological sample, and (2) comparing the expression level determined in step (1) with a control level, wherein an increase in expression level as compared to a normal control level indicates that said subject suffers from ovarian endometriosis and a similarity of said expression level as compared to a disease control level indicates that said subject suffers from ovarian endometriosis.    
     
     
         19 . The method of  claim 18 , wherein the expression level is determined by immunoassay.  
     
     
         20 . The method of  claim 19 , wherein the immunoassay is ELISA.  
     
     
         21 . The method of  claim 20 , wherein a polyclonal antibody and a monoclonal antibody against the TFPI-2 protein is used as the labeled antibody and immobilized antibody, respectively, for ELISA.  
     
     
         22 . The method of  claim 18 , wherein the biological sample is blood or a blood-derived sample.  
     
     
         23 . A kit for diagnosing ovarian endometriosis comprising one or more antibodies binding to a TFPI-2 protein.  
     
     
         24 . The kit of  claim 23 , which comprises (1) a detectably labeled antibody binding to the TFPI-2 protein, and (2) an antibody binding to the TFPI-2 protein that is immobilized on a solid matrix.  
     
     
         25 . The kit of  claim 24 , wherein the detectably labeled antibody is polyclonal and the antibody immobilized on a solid matrix is monoclonal.  
     
     
         26 . The kit of  claim 23 , which comprises (1) a detectably labeled antibody binding to the TFPI-2 protein, (2) an antibody binding to the TFPI-2 protein which may be immobilized on a matrix, and (3) a reagent for immobilizing the antibody of (2) on a matrix.  
     
     
         27 . The kit of  claim 26 , wherein the detectably labeled antibody is polyclonal and the antibody that may be immobilized on a solid matrix is monoclonal.  
     
     
         28 . The kit of  claim 23 , wherein the kit further comprises either or both of normal control sample and endometriosis control sample.